The objectives of this research are to further our understanding of the molecular basis for the regulation of metabolism by hormones and other regulatory agents. The regulation of glycogen metabolism will be stressed but mechanisms revealed by research in this area will be applied to other aspects of cellular function. Of particular importance will be a study of skeletal muscle protein kinases which will be examined from the standpoint of multimolecular forms, specificity, activation by cyclic AMP, and their quaternary structure. Two of the substrates for cyclic AMP-dependent protein kinases, phosphorylase kinase and glycogen synthetase, will be characterized as to the possible structural similarity of their phosphate-binding sites, and the relationship between phosphorylation and changes in enzyme activity will be studied for each enzyme. A detailed study of the functions of the different subunits of phosphorylase kinase will be made with the end in view of determining whether this enzyme contains separate catalytic and regulatory subunits. New substrates for cyclic AMP-dependent protein kinases will be sought in skeletal muscle and in other mammalian tissues. Specific and nonspecific phosphoprotein phosphatases will be isolated and characterized as to their specificity and possible regulation by covalent alteration.